Genetic Variant PARVB:c.774+547C>T (chr22-44148469-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013327.5(PARVB):c.774+547C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 163,264 control chromosomes in the GnomAD database, including 2,571 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2443 hom., cov: 33)

Exomes 𝑓: 0.10 ( 128 hom. )

Consequence

PARVB
NM_013327.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.647

Publications

1 publications found

Variant links:

Genes affected

PARVB (HGNC:14653): (parvin beta) This gene encodes a member of the parvin family of actin-binding proteins, which play a role in cytoskeleton organization and cell adhesion. These proteins are associated with focal contacts and contain calponin homology domains that bind to actin filaments. This family member binds to alphaPIX and alpha-actinin, and it can inhibit the activity of integrin-linked kinase. This protein also functions in tumor suppression. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

PARVB links:

ENSG00000280434 (HGNC:):

ENSG00000280434 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013327.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PARVB	NM_013327.5	MANE Select	c.774+547C>T	intron	N/A	NP_037459.2
PARVB	NM_001003828.3		c.873+547C>T	intron	N/A	NP_001003828.1	Q9HBI1-2
PARVB	NM_001243385.2		c.663+547C>T	intron	N/A	NP_001230314.1	Q9HBI1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PARVB	ENST00000338758.12	TSL:1 MANE Select	c.774+547C>T	intron	N/A	ENSP00000342492.6	Q9HBI1-1
PARVB	ENST00000406477.7	TSL:1	c.873+547C>T	intron	N/A	ENSP00000384515.3	Q9HBI1-2
PARVB	ENST00000404989.1	TSL:1	c.663+547C>T	intron	N/A	ENSP00000384353.1	Q9HBI1-3

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22262

AN:

152088

Hom.:

2436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.0843

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0551

Gnomad OTH

AF:

0.139

GnomAD4 exome

AF:

0.105

AC:

1156

AN:

11058

Hom.:

128

Cov.:

AF XY:

0.113

AC XY:

650

AN XY:

5754

show subpopulations

African (AFR)

AF:

0.237

AC:

AN:

190

American (AMR)

AF:

0.197

AC:

485

AN:

2458

Ashkenazi Jewish (ASJ)

AF:

0.0714

AC:

AN:

112

East Asian (EAS)

AF:

0.133

AC:

106

AN:

796

South Asian (SAS)

AF:

0.223

AC:

291

AN:

1306

European-Finnish (FIN)

AF:

0.0517

AC:

AN:

174

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0334

AC:

187

AN:

5596

Other (OTH)

AF:

0.0598

AC:

AN:

418

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

137

183

229

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.146

AC:

22292

AN:

152206

Hom.:

2443

Cov.:

AF XY:

0.153

AC XY:

11385

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.280

AC:

11617

AN:

41502

American (AMR)

AF:

0.193

AC:

2955

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

368

AN:

3468

East Asian (EAS)

AF:

0.166

AC:

858

AN:

5174

South Asian (SAS)

AF:

0.308

AC:

1487

AN:

4828

European-Finnish (FIN)

AF:

0.0843

AC:

895

AN:

10612

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0551

AC:

3750

AN:

68012

Other (OTH)

AF:

0.138

AC:

291

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

904

1808

2712

3616

4520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0914

Hom.:

840

Bravo

AF:

0.159

Asia WGS

AF:

0.246

AC:

853

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.0

(source)

DANN

Benign

0.68

PhyloP100

-0.65

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over